PubMed1993
Voltage-dependent effects of YC-170, a dihydropyridine derivative, on rabbit cardiac L-type Ca2+ channels were investigated and compared with those of a dihydropyridine Ca2+ agonist, BAY K 8644, using patch clamp techniques. Single Ca2+ channel activities were elicited by depolarizing pulses to O mV from holding potentials (HPs) of -80 mV and -40 mV. With a HP of -80 mV, YC -170 (10 microM) increased a mean open time of the Ca2+ channel (vector o) from 0.50 +/- 0.03 ms to 1.2 +/- 0.05 ms (mean +/- S.E., n = 5), and increased NPo value of the Ca2+ channel by 710 +/- 96% (n = 5) of the control value. On the other hand, with a HP of -40 mV, YC-170 had little effects on NPo value (94 +/- 6.6% of the control value, n = 5), although YC-170 increased vector o from 0.64 +/- 0.05 ms to 1.2 +/- 0.11 ms. BAY K 8644 increased NPo values to almost the same degree with both HPs (920 +/- 93% with a HP of -80 mV, n = 5, and 990 +/- 85% with a HP of -40 mV, n = 5). BAY K 8644 (1 microM) remarkably increased vector o with both HPs (from 0.66 +/- 0.09 ms to 3.3 +/- 0.50 ms, n = 3, with a HP of -80 mV and from 0.68 +/- 0.06 ms to 4.9 +/- 1.2 ms, n = 4, with a HP of -40 mV). Although YC-170 and BAY K 8644 increased vector o with both HPs, YC-170 failed to produce the Ca2+ agonistic effect with less negative HP (-40 mV). Thus, another mechanism differing from prolongation of the open time may be involved in the agonistic action of YC-170. YC-170 increased markedly the frequency of openings of Ca2+ channels with a HP of -80 mV and decreased it with a HP of -40 mV. BAY K 8644 increased it slightly with a HP of -40 mV and did not change it with a HP of -80 mV. Analysis using closed time histograms also revealed that YC-170 enhanced reopenings of Ca2+ channels with a HP of 80 mV and suppressed it with a HP of -40 mV, BAY K 8644 enhanced it with both HPs. Two mechanisms may be involved in the agonistic action of dihydropyridine Ca2+ agonists. One is prolongation of the open time of Ca2+ channels and the other is an enhancement of reopenings of Ca2+ channels. The former mechanism may not be voltage dependent and the latter mechanism may be voltage dependent.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗